Project description:PHF13 is a H3K4me3 epigenetic reader, that modulates key chromatin processes including transcription, DNA damage response and chromatin architecture. PHF13 is found aberrantly regulated in different cancers and its misexpression alters the epigenetic landscape of key transcription factors that regulate Epithelial to Mesenchymal transition. In this study we sought to understand how PHF13’s chromatin affinity and diverse chromatin functions are intrinsically regulated. Our results show that PHF13 can oligomerize via conserved ordered regions in its N- and C- terminus increasing its chromatin valence and avidity. Impressively, a 4-fold over expression of PHF13 was sufficient to globally compact chromatin, dependent on its ordered dimerizing regions and oligomerization potential. Unexpectedly, we discovered that PHF13 can self-associate independent of its ordered domains via intrinsically disordered regions, which conversely reduced PHF13’s chromatin affinity. Our findings support that there is an intrinsic balance between PHF13’s ordered and disordered regions that regulates PHF13 chromatin affinity, and suggest that PHF13 can phase transition between polymer-polymer and liquid-liquid phase separation states to impact chromatin structure and function.
Project description:PHF13 is a H3K4me3 epigenetic reader, that modulates key chromatin processes including transcription, DNA damage response and chromatin architecture. PHF13 is found aberrantly regulated in different cancers and its misexpression alters the epigenetic landscape of key transcription factors that regulate Epithelial to Mesenchymal transition. In this study we sought to understand how PHF13’s chromatin affinity and diverse chromatin functions are intrinsically regulated. Our results show that PHF13 can oligomerize via conserved ordered regions in its N- and C- terminus increasing its chromatin valence and avidity. Impressively, a 4-fold over expression of PHF13 was sufficient to globally compact chromatin, dependent on its ordered dimerizing regions and oligomerization potential. Unexpectedly, we discovered that PHF13 can self-associate independent of its ordered domains via intrinsically disordered regions, which conversely reduced PHF13’s chromatin affinity. Our findings support that there is an intrinsic balance between PHF13’s ordered and disordered regions that regulates PHF13 chromatin affinity, and suggest that PHF13 can phase transition between polymer-polymer and liquid-liquid phase separation states to impact chromatin structure and function.
Project description:We investigated the role of PHF13 in TGFβ-induced Epithelial-to-Mesenchymal Transition and found PHF13 is essential for TGFβ-promoted broadest H3K4me3 domains and super-enhancers activation.
Project description:We report expression profiles for mouse testes carrying a Phf13 knockout in comparison to wildtype testes. Upregulation of X- and Y-linked genes is evident after loss of PHF13.
Project description:We recently identified the nonreceptor tyrosine kinase syk as a tumor suppressor in pancreatic ductal adenocarcinoma cells. Reintroduction of syk into Panc1 cells promoted a more differentiated phenotype and retarded invasion and tumorigenic growth. Gene array analysis identified over 2,000 transcripts differentially expressed at FDR<0.01. Among these were members of the MMP2 axis, which were subsequently shown to regulate Panc1 invasion. Experiment Overall Design: Affymetrix global gene arrays were used to analyse differences in gene expression patterns in Panc1 cells stably reexpressing syk, or vector-only mock controls. RNA was harvested from cells grown under identical conditions in standard culture.
Project description:We investigated the role of PHF13 in TGFβ-induced Epithelial-to-Mesenchymal Transition and found PHF13 is essential for TGFβ-promoted broadest H3K4me3 domains and super-enhancers activation.
Project description:The effects of mutant p53 on TNFa stimulated PANC1 cells was tested. PANC1 cell harbor endogenous mutation in p53 (R273H). We knocked down this mutp53 (using sirna for p53) and then treated with low doses of TNFa to detect any differential transcription regulation governed by mutp53.
Project description:The effects of mutant p53 on TNFa stimulated PANC1 cells was tested. PANC1 cell harbor endogenous mutation in p53 (R273H). We knocked down this mutp53 (using sirna for p53) and then treated with low doses of TNFa to detect any differential transcription regulation governed by mutp53. A total of 7 samples, 3 of them were duplicated
